The Development of Irreversible Inhibition for Metallo-.BETA.-Lactamase (IMP-1)
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Accession number;06A0759482
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| Title;The Development of Irreversible Inhibition for Metallo-.BETA.-Lactamase (IMP-1) |
| Author;
YAMAGUCHI YOSHIHIRO
(Kumamoto Univ., JPN)
KUROSAKI HIROMASA
(Kumamoto Univ., Graduate School of Medical and Pharmaceutical Sciences, JPN)
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Journal Title;Journal of the Crystallographic Society of Japan
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Journal Code:G0232A
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ISSN:0369-4585
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VOL.48;NO.4;PAGE.259-264(2006)
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| Figure&Table&Reference;FIG.7, TBL.1, REF.19 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Pathogenic bacteria that produce metallo-.BETA.-lactamases (MBLs) are emerging as a new threat to the medical community. These enzymes catalyze the hydrolysis of almost .BETA.-lactam antibiotics. Moreover, serine-.BETA.-lactamase inhibitors are ineffective against MBLs. Thus, the development of inhibitors for MBLs is important. We prepared two inhibitors, pentafluorophenyl 3-mercaptopropionate (PFMP, 1) and 3-(3-mercaptopropionylsulfanyl)propionic acid pentafluorophenyl ester (MPAP, 2) for one of MBLs, IMP-1. From the gel-filtration experiment of the enzyme-inhibitor complex, these compounds inhibited IMP-1 irreversibly. Moreover, X-ray crystallography revealed that inhibitor 2 covalently binds to IMP-1 to form an amide bond between the amino group (N'.ZETA.') of Lys224 and the inhibitor. (author abst.) |
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